The flow pattern of the short gastric veins that drain the fundic portion of the stomach appeared to influence mammary tumorigenesis. In I and C57BL mice, strains that are highly resistant to murine mammary tumor virus (MuMTV)-induced mammary tumorigenesis, the short gastric veins empty directly into the splenic vein outside the spleen, connecting with the portal system. In (C57BL X I)F1 mice, which are highly susceptible to MuMTV-induced mammary tumorigenesis, the short gastric veins empty directly into the superior hilus of the spleen, connecting with the splenic parenchyma. Neonatal splenectomy or cauterization of the short gastric veins of (C57BL X I)F1 mice prior to the introduction of MuMTV by foster-nursing delayed the onset and reduced the final incidence of mammary tumors. When neonatal splenectomy was performed after milk-borne MuMTV introduction, it caused premature appearance of mammary tumors without affecting the final tumor incidence. In A, BALB/c, C3H, DBA/2, GR, and RIII mice, strains that are susceptible to MuMTV-induced mammary tumorigenesis, the short gastric veins also empty into the superior hilus of the spleen. Our findings suggest that susceptibility to mammary taumorigenesis may depend on the direct entry of milk-borne MuMTV into the splenic environment through the short gastric veins that drain the fundus of the stomach.